Field of the Invention
This invention is concerned with new organic compounds and more particularly with triazinobenzodiazepines and methods for the production thereof.
The new products of this invention and the process of production thereof can be illustratively represented by the following formulae: ##STR4## If R.sub.1 is --(CH.sub.2).sub.n A' (A' is X and X is chloro or bromo) and ##STR5## wherein R and R.sub.2 are hydrogen or methyl; wherein R.sub.1 is --COOH; COOR', in which R' is alkyl of 1 to 3 carbon atoms, inclusive, --(CnH.sub.2 n)A in which A is fluoro, chloro, bromo, hydroxy, or alkoxy in which the alkyl group is defined as above; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl, or nitro, and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, or 2-pyridyl, and wherein X is chlorine or bromine, and wherein Y is chloro, bromo, iodo, or --O--SO.sub.2 R.sub.4 (R.sub.4 is alkyl of 1-3 carbon atoms, phenyl, or tolyl) and wherein R" and R'" are hydrogen or alkyl defined as above or together ##STR6## is pyrrolidino, piperidino, morpholino, 4-methylpiperazino, or 4-(2-hydroxymethyl)piperazino.
The invention therefore comprises compounds of formula IV ##STR7## wherein R and R.sub.2 are hydrogen or methyl; wherein R.sub.1 is --COOH, COOR' in which R' is alkyl of 1 to 3 carbon atoms, inclusive, --(CnH.sub.2 n)A in which n is an integer of 1 to 3 and A is fluoro, chloro, bromo, hydroxy, alkoxy in which the alkyl group is defined as above, or ##STR8## in which R" and R'" are hydrogen or alkyl as defined above or together ##STR9## is pyrrolidino, piperidino, morpholino, 4-methylpiperazino, or 4-(2-hydroxyethyl)-piperazino; wherein R.sub.3 is hydrogen, fluoro, chloro, bromo, trifluoromethyl, or nitro, and wherein Ar is phenyl, o-chlorophenyl, o-fluorophenyl, 2,6-difluorophenyl, or 2-pyridyl.
The invention also encompasses besides the compounds of formula IV, the pharmacologically acceptable acid addition salts of these compounds.
The more desirable products of this invention have the formula IVA ##STR10## wherein A' is hydroxy or ##STR11## in which R.sub.o and R'.sub.o are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; wherein n is an integer of 1 to 3; wherein R'.sub.3 is hydrogen, chloro, fluoro, or trifluoromethyl; wherein R.sub.4 is hydrogen, chloro, or fluoro; and wherein R.sub.5 is hydrogen or fluoro with the proviso that R.sub.5 is not fluoro if R.sub.4 is chloro, and the pharmacologically acceptable acid addition salts thereof.
The most desirable compounds of this invention are of the formula IVB ##STR12## wherein A" is hydroxy or dimethylamino, R".sub.3 and R.sub.4 are hydrogen, chloro, or fluoro, and the pharmacologically acceptable acid addition salts thereof.
The process of the present invention comprises: treating a compound of formula I with a reagent of formula II to give the corresponding 2-(substituted-hydrazino)benzodiazepine III; and heating III to cyclize it and to provide the corresponding final product IV. If, as final product, a compound is desired wherein A is ##STR13## a compound wherein R.sub.1 is --(CnH.sub.2 n)X in which n is 1 to 3 and X is chloro or bromo can be reacted with a selected secondary amine in conventional manner.